tbuckley/cabot-search huggingface dataset:
Fluid Resuscitation in Acute Pancreatitis — Going over the WATERFALL
Authors: Timothy B. Gardner
Journal: New England Journal of Medicine (2022)

Acute pancreatitis, responsible for approximately 300,000 hospital admissions in the United States annually, is characterized by intense inflammation of the pancreas that leads to severe disease in approximately one third of affected patients.1 Because no proven pharmacologic therapy for acute pancreatitis exists, treatment is largely supportive.2 Intravenous fluid resuscitation is recommended as a fundamental component of initial supportive therapy in acute pancreatitis, owing largely to observations that untreated pancreatic hypoperfusion contributes to poor outcomes such as pancreatic necrosis and death.3 For the past three decades, multiple studies — but few randomized, controlled trials — have investigated the effects of crystalloid . . .
Protease‐Sensitive, VEGF‐Mimetic Peptide, and IKVAV Laminin‐Derived Peptide Sequences within Elastin‐Like Recombinamer Scaffolds Provide Spatiotemporally Synchronized Guidance of Angiogenesis and Neurogenesis
Authors: Fernando González‐Pérez, Matilde Alonso, Israel González de Torre, Mercedes Santos, José Carlos Rodríguez‐Cabello
Journal: Advanced Healthcare Materials (2022)

Spatiotemporal control of vascularization and innervation is a desired hallmark in advanced tissue regeneration. For this purpose, we design a 3D model scaffold, based on elastin-like recombinamer (ELR) hydrogels. This contains two interior and well-defined areas, small cylinders, with differentiated bioactivities with respect to the bulk. Both are constructed on a protease sensitive ELR with a fast-proteolyzed domain, but one bears a VEGF-mimetic peptide (QK) and the other a laminin-derived pentapeptide (IKVAV), to promote angiogenesis and neurogenesis, respectively. The outer bulk is based on a slow proteolytic sequence and RGD cell adhesion domains. In vitro studies show the effect of QK and IKVAV peptides on the promotion of endothelial cell and axon spreading, respectively. The subcutaneous implantation of the final 3D scaffold demonstrates the ability to spatiotemporally control angiogenesis and neurogenesis in vivo. Specifically, the inner small cylinder containing the QK peptide promotes fast endothelialization, whereas the one with IKVAV peptide promotes fast neurogenesis. Both, vascularization and innervation take place in advance of the bulk scaffold infiltration. This scaffold shows that it is possible to induce vascularization and innervation in predetermined areas of the scaffold well ahead to the bulk infiltration. That significantly increases the efficiency of the regenerative activity.
Effectiveness and Durability of the BNT162b2 Vaccine against Omicron Sublineages in South Africa
Authors: Shirley Collie, Jiren Nayager, Lesley Bamford, Linda-Gail Bekker, Matt Zylstra, Glenda Gray
Journal: New England Journal of Medicine (2022)

Effectiveness and Durability of the BNT162b2 Vaccine against Omicron Sublineages in South AfricaTo the Editor: Data are limited regarding the effectiveness of the BNT162b2 vaccine (Pfizer-BioNTech) against the BA.4 and BA.5 sublineages of the B.1.1.529(omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that drove the recent fifth wave of infection in South Africa. 1 We previously reported a vaccine effectiveness of 70% after two doses of the BNT162b2 vaccine against severe disease during the fourth wave of omicron infection driven by the BA.1 sublineage in South Africa. 1,2 In this analysis, we separately assessed the effectiveness and durability of the BNT162b2 vaccine against BA.1 or BA.2 and against BA.4 or BA.5 among members of Discovery Health, a medical care organization that provides health insurance to 3.7 million persons in South Africa.During the period from November 15, 2021, to June 24, 2022, a total of 32,883 patients who had been hospitalized for medical treatment underwent polymerase-chain-reaction testing for SARS-CoV-2, a period that spanned the BA.1-BA.2 and BA.4-BA.5 omicron waves.Of these patients, * In South Africa, the BA.1 and BA.2 sublineages of the omicron variant were dominant from November 15, 2021, to February 28, 2022; the BA.4 and BA.5 sublineages were dominant from April 15 to June 24, 2022.Estimates of vaccine effectiveness (VE) are provided only if the P value was less than 0.05 for the between-group difference in the calculation of the odds ratio from the test-negative case-control design, if the number of polymerase-chain-reaction assays on admission was available, and if more than 10 admissions were observed for the estimate.Estimates of vaccine effectiveness have not been adjusted for multiplicity.CI denotes confidence interval.
Treatment for Appendicitis
Authors: Zu-Kai Wang, Ying-Qi Huang, Qi-Chen He
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
In situ delivery of nanoparticles formulated with micron-sized crystals protects from murine melanoma
Authors: Mona O Mohsen, Matthew Heath, Matthias F Kramer, Thalia Carreno Velazquez, Alan Bullimore, Murray A Skinner, Daniel E Speiser, Martin F Bachmann
Journal: Journal for ImmunoTherapy of Cancer (2022)

Introduction Intratumoral injections of novel therapeutics can activate tumor antigen-specific T cells for locoregional tumor control and may even induce durable systemic protection (against distant metastases) via recirculating T cells. Here we explored the possibility of a universal immunotherapy that promotes T-cell responses in situ and beyond, upon intratumoral injection of nanoparticles formulated with micron-sized crystals. Methods Cucumber mosaic virus-like particles containing a tetanus toxin peptide (CuMV TT ) were formulated with microcrystalline tyrosine (MCT) adjuvant and injected directly in B16F10 melanoma tumors. To further enhance immunogenicity, we loaded the nanoparticles with a TLR7/8 ligand and incorporated a universal tetanus toxin T-helper cell peptide. We assessed therapeutic efficacy and induction of local and systemic immune responses, including RNA sequencing, providing broad insight into the tumor microenvironment and correlates of protection. Results MCT crystals were successfully decorated with CuMV TT nanoparticles. This ‘immune-enhancer’ formed immunogenic depots in injected tumors, enhanced polyfunctional CD8 + and CD4 + T cells, and inhibited B16F10 tumor growth locally and systemically. Local inflammation and immune responses were associated with upregulation of genes involved in complement activation and collagen formation. Conclusions Our new immune-enhancer turned immunologically cold tumors into hot ones and inhibited local and distant tumor growth. This type of immunotherapy does not require the identification of (patient–individual) relevant tumor antigens. It is well tolerated, non-infectious, and affordable, and can readily be upscaled for future clinical testing and broad application in melanoma and likely other solid tumors.
A protein encoded by circular ZNF609 RNA induces acute kidney injury by activating the AKT/mTOR-autophagy pathway
Authors: Xin Ouyang, Zhimei He, Heng Fang, Huidan Zhang, Qi Yin, Linhui Hu, Fei Gao, Hao Yin, Taofang Hao, Yating Hou, Qingrui Wu, Jia Deng, Jing Xu, Yirong Wang, Chunbo Chen
Journal: Molecular Therapy (2022)
Effect of S14.S-nm Argon Ion Laser Radiation on Hematoporphyrin Derivative-Treated Bladder Tumor Cells In Vitro and In Vivo&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: David A. Bellnier
 4, George R. Prout, Jr., Chi-Wei Lin
Journal: JNCI Journal of the National Cancer Institute (1985)

The therapeutic effect of hematoporphyrin derivative (HpD) plus 514.5-nm argon ion laser radiation was compared to HpD plus 630-nm argon ion laser-pumped dye laser radiation in experimental urinary bladder transitional cell carcinoma models. Cultured human bladder cancer cells (EJ) containing HpD were 2.8-fold more sensitive to 514.5-nm radiation than to 630-nm radiation as measured by clonogenic capacity. The relative effectiveness of 514.5-nm versus 630-nm light was approximately proportional to the spectral absorbance for cell-bound HpD at these wavelengths. HpD-sensitized photoirradiation was studied in solid tumors produced by a) the subcutaneous inoculation of cells from murine bladder tumors induced by N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide (CAS: 24554-26-5) into female C3H mice (MBT -2 tumor) and b) the intravesical instillation of N-methyl-N-nitrosourea (CAS: 684-93-5) into the urinary bladders of female Wistar rats. The tumors were exposed to 144 J/cm2 laser light 24–48 hours following ip injection of 20 mg HpD/kg body weight. By 24–48 hours, animals that received HpD and light of either wavelength had partially or completely necrosed tumors. Control groups showed no necrotic changes. Regression of MBT-2 tumors was also investigated. Seven of 14 and 6 of 12 animals had nonpalpable tumors 1 week after treatment with 514.5-nm and 630-nm light, respectively. Tumors in control groups demonstrated no regression. Spectral transmittance from 630 nm to 514.5 nm decreased by about 4% for 130- to 160-µm-thick sections of canine urothelium and bladder submucosa-muscularis. The results of this study indicate that HpD plus 514.5-nm laser radiation may be an effective treatment for small or superficial malignant lesions of the urinary bladder.
Deep Learning of Coronary Calcium Scores From PET/CT Attenuation Maps Accurately Predicts Adverse Cardiovascular Events
Authors: Konrad Pieszko, Aakash Shanbhag, Aditya Killekar, Robert J.H. Miller, Mark Lemley, Yuka Otaki, Ananya Singh, Jacek Kwiecinski, Heidi Gransar, Serge D. Van Kriekinge, Paul B. Kavanagh, Edward J. Miller, Timothy Bateman, Joanna X. Liang, Daniel S. Berman, Damini Dey, Piotr J. Slomka
Journal: JACC. Cardiovascular imaging (2022)
Major Global Coronary Artery Calcium Guidelines
Authors: Ilana S. Golub, Orly G. Termeie, Stephanie Kristo, Lucia P. Schroeder, Suvasini Lakshmanan, Ahmed M. Shafter, Luay Hussein, Dhiran Verghese, Jairo Aldana-Bitar, Venkat S. Manubolu, Matthew J. Budoff
Journal: JACC. Cardiovascular imaging (2022)
CAD-RADS™ 2.0 – 2022 Coronary Artery Disease-Reporting and Data System
Authors: Ricardo C. Cury, Jonathon Leipsic, Suhny Abbara, Stephan Achenbach, Daniel Berman, Marcio Bittencourt, Matthew Budoff, Kavitha Chinnaiyan, Andrew D. Choi, Brian Ghoshhajra, Jill Jacobs, Lynne Koweek, John Lesser, Christopher Maroules, Geoffrey D. Rubin, Frank J. Rybicki, Leslee J. Shaw, Michelle C. Williams, Eric Williamson, Charles S. White, Todd C. Villines, Ron Blankstein
Journal: JACC. Cardiovascular imaging (2022)
Impact of Loading and Myocardial Mechanical Properties on Natural Shear Waves
Authors: Stéphanie Bézy, Jürgen Duchenne, Marta Orlowska, Annette Caenen, Matthew Amoni, Sebastian Ingelaere, Laurine Wouters, Keir McCutcheon, Lennert Minten, Alexis Puvrez, Jan D’hooge, Jens-Uwe Voigt
Journal: JACC. Cardiovascular imaging (2022)
Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank
Authors: Zahra Raisi-Estabragh, Celeste McCracken, Evan Hann, Dorina-Gabriela Condurache, Nicholas C. Harvey, Patricia B. Munroe, Vanessa M. Ferreira, Stefan Neubauer, Stefan K. Piechnik, Steffen E. Petersen
Journal: JACC. Cardiovascular imaging (2022)

Cardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied. The associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up. Native T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models. Higher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310). This large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.
Multi-Imaging Characterization of Cardiac Phenotype in Different Types of Amyloidosis
Authors: Adam Ioannou, Rishi K. Patel, Yousuf Razvi, Aldostefano Porcari, Daniel Knight, Ana Martinez-Naharro, Tushar Kotecha, Lucia Venneri, Liza Chacko, James Brown, Charlotte Manisty, James Moon, Brendan Wisniowski, Helen Lachmann, Ashutosh Wechelakar, Carol Whelan, Peter Kellman, Philip N. Hawkins, Julian D. Gillmore, Marianna Fontana
Journal: JACC. Cardiovascular imaging (2022)

Bone scintigraphy is extremely valuable when assessing patients with suspected cardiac amyloidosis (CA), but the clinical significance and associated phenotype of different degrees of cardiac uptake across different types is yet to be defined.This study sought to define the phenotypes of patients with varying degrees of cardiac uptake on bone scintigraphy, across multiple types of systemic amyloidosis, using extensive characterization comprising biomarkers as well as echocardiographic and cardiac magnetic resonance (CMR) imaging.A total of 296 patients (117 with immunoglobulin light-chain amyloidosis [AL], 165 with transthyretin amyloidosis [ATTR], 7 with apolipoprotein AI amyloidosis [AApoAI], and 7 with apolipoprotein AIV amyloidosis [AApoAIV]) underwent deep characterization of their cardiac phenotype.AL patients with grade 0 myocardial radiotracer uptake spanned the spectrum of CMR findings from no CA to characteristic CA, whereas AL patients with grades 1 to 3 always produced characteristic CMR features. In ATTR, the CA burden strongly correlated with myocardial tracer uptake, except in Ser77Tyr. AApoAI presented with grade 0 or 1 and disproportionate right-sided involvement. AApoAIV always presented with grade 0 and characteristic CA. AL grade 1 patients (n = 48; 100%) had characteristic CA, whereas only ATTR grade 1 patients with Ser77Tyr had characteristic CA on CMR (n = 5; 11.4%). After exclusion of Ser77Tyr, AApoAI, and AApoAIV, CMR showing characteristic CA or an extracellular volume of >0.40 in patients with grade 0 to 1 cardiac uptake had a sensitivity and specificity of 100% for AL.There is a wide variation in cardiac phenotype between different amyloidosis types across different degrees of cardiac uptake. The combination of CMR and bone scintigraphy can help to define the diagnostic differentials and the clinical phenotype in each individual patient.
Tafamidis Decreases Cardiac Uptake of 99mTc-HMDP in Transthyretin Cardiac Amyloidosis
Authors: Shirley Odouard, Mukedaisi Abulizi, Mounira Kharoubi, Silvia Oghina, Soulef Guendouz, Amira Zaroui, Emmanuel Teiger, Emmanuel Itti, Thibaud Damy, Arnault Galat
Journal: JACC. Cardiovascular imaging (2022)
Human infection of avian influenza A H3N8 virus and the viral origins: a descriptive study
Authors: Rengui Yang, Honglei Sun, Feng Gao, Kaiwei Luo, Zheng Huang, Qi Tong, Hao Song, Qiqi Han, Jiyu Liu, Yu Lan, Jianxun Qi, Han Li, Shuilian Chen, Mingzhong Xu, Jinsong Qiu, Ge Zeng, Xixing Zhang, Chaoyang Huang, Ruiqing Pei, Zhifei Zhan, Beiwei Ye, Yaxin Guo, Yinzhu Zhou, Wen Ye, Dong Yao, Min Ren, Bo Li, Jizhe Yang, Yanan Wang, Juan Pu, Yipeng Sun, Yi Shi, William J Liu, Xinhua Ou, George F Gao, Lidong Gao, Jinhua Liu
Journal: The Lancet Microbe (2022)
Visual Presence of Mechanical Dyssynchrony Combined With Septal Scarring Identifies Responders to Cardiac Resynchronization Therapy
Authors: Jürgen Duchenne, Camilla K. Larsen, Marta Cvijic, Elena Galli, John M. Aalen, Boudewijn Klop, Alexis Puvrez, Oana Mirea, Stéphanie Bézy, Lennert Minten, Per Anton Sirnes, Faraz H. Khan, Gabor Voros, Rik Willems, Martin Penicka, Erik Kongsgård, Einar Hopp, Jan Bogaert, Otto A. Smiseth, Erwan Donal, Jens-Uwe Voigt
Journal: JACC. Cardiovascular imaging (2022)
Follow-Up Cardiovascular Magnetic Resonance Findings in Patients With COVID-19 Vaccination-Associated Acute Myocarditis
Authors: Yash R. Patel, Nishant R. Shah, Kristin Lombardi, Saurabh Agarwal, Gregory Salber, Rootu Patel, Athena Poppas, Michael K. Atalay
Journal: JACC. Cardiovascular imaging (2022)
Novel technologies to characterize and engineer the microbiome in inflammatory bowel disease
Authors: Alba Boix-Amorós, Hilary Monaco, Elisa Sambataro, Jose C. Clemente
Journal: Gut Microbes (2022)

We present an overview of recent experimental and computational advances in technology used to characterize the microbiome, with a focus on how these developments improve our understanding of inflammatory bowel disease (IBD). Specifically, we present studies that make use of flow cytometry and metabolomics assays to provide a functional characterization of microbial communities. We also describe computational methods for strain-level resolution, temporal series, mycobiome and virome data, co-occurrence networks, and compositional data analysis. In addition, we review novel techniques to therapeutically manipulate the microbiome in IBD. We discuss the benefits and drawbacks of these technologies to increase awareness of specific biases, and to facilitate a more rigorous interpretation of results and their potential clinical application. Finally, we present future lines of research to better characterize the relation between microbial communities and IBD pathogenesis and progression.
Imaging sensitive and drug-resistant bacterial infection with [11C]-trimethoprim
Authors: Iris K. Lee, Daniel A. Jacome, Joshua K. Cho, Vincent Tu, Anthony J. Young, Tiffany Dominguez, Justin D. Northrup, Jean M. Etersque, Hsiaoju S. Lee, Andrew Ruff, Ouniol Aklilu, Kyle Bittinger, Laurel J. Glaser, Daniel Dorgan, Denis Hadjiliadis, Rahul M. Kohli, Robert H. Mach, David A. Mankoff, Robert K. Doot, Mark A. Sellmyer
Journal: Journal of Clinical Investigation (2022)

BACKGROUND. Several molecular imaging strategies can identify bacterial infections in humans. PET affords the potential for sensitive infection detection deep within the body. Among PET-based approaches, antibiotic-based radiotracers, which often target key bacterial-specific enzymes, have considerable promise. One question for antibiotic radiotracers is whether antimicrobial resistance (AMR) reduces specific accumulation within bacteria, diminishing the predictive value of the diagnostic test.
Risk factors for prolonged recovery from concussion in young patients
Authors: Steven Cuff, Aaron Maki, Robyn Feiss, Julie Young, Junxin Shi, Amanda Hautmann, Jingzhen Yang
Journal: British Journal of Sports Medicine (2022)

For young patients sustaining concussion, assessing recovery is vital in determining safe return to play. Identifying risk factors may aid clinicians in recognising patients at risk for prolonged recovery. The study objective is to identify risk factors for prolonged (>28 days) and extended (>90 days) recovery (defined as symptom duration) and analyse how these risk factors differ between the two groups.We retrospectively analysed electronic health record data (n=4937) among patients aged 10-18 years collected at Nationwide Children's Hospital Sports Medicine concussion clinics between 1 July 2012 and 30 June 2019. Data collected included patient demographics, comorbidities (eg, prior psychiatric diagnoses, prior concussions) and injury characteristics (eg, loss of consciousness, injury setting). We examined patient risk factors for prolonged (>28 days) and/or extended (>90 days) recovery using modified Poisson regression models.Factors associated with increased risk of prolonged recovery from concussion included prior concussions (adjusted risk ratio (ARR) 1.19, 95% CI 1.02 to 1.38) for two concussions (ARR 1.36, 95% CI 1.14 to 1.61), for >3, and higher initial symptom score (ARR 2.57, 95% CI 2.34 to 2.83) for postconcussion symptom (PCS) scores 21-60 (ARR 2.89, 95% CI 2.54 to 3.29), for PCS>60. Risk factors for extended recovery included history of concussion (ARR 1.50, 95% CI 1.09 to 2.06) for two concussions (ARR 1.75, 95% CI 1.17 to 2.62), for >3 and older age (15-18 years, ARR 1.11, 95% CI 1.05 to 1.18). Additionally, comorbid attention deficit hyperactivity disorder increased risk of prolonged recovery (ARR 1.14, 95% CI 1.01 to 1.29) while anxiety increased risk for extended recovery (ARR 1.47, 95% CI 1.10 to 1.95).Overall, risk factors for prolonged recovery differ somewhat from risk factors for extended recovery. For patients who present to clinic with concussion, mental health is an important consideration which may impact the timeline for symptom recovery.
EULAR 75-year anniversary: commentaries on<i>ARD</i>papers from 25 years ago
Authors: Kimme L Hyrich
Journal: Annals of the Rheumatic Diseases (2022)

Neural stem/progenitor cells (NSPCs) of the ventricular–subventricular zone (V-SVZ) are candidate cells of origin for many brain tumors. However, whether NSPCs in different locations within the V-SVZ differ in susceptibility to tumorigenic mutations is unknown. Here, single-cell measurements of signal transduction intermediates in the mechanistic target of rapamycin complex 1 (mTORC1) pathway reveal that ventral NSPCs have higher levels of signaling than dorsal NSPCs<i>.</i> These features are linked with differences in mTORC1-driven disease severity: introduction of a pathognomonic <i>Tsc2</i> mutation only results in formation of tumor-like masses from the ventral V-SVZ. We propose a direct link between location-dependent intrinsic growth properties imbued by mTORC1 and predisposition to tumor development.